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Guide for post-exposure prophylaxis

The recommendations given here are intended as a general guide. It is recognized that, in certain situations, modifications of the procedures laid down may be warranted. Such situations include exposure of infants or mentally disabled persons and other circumstances where a reliable history cannot be obtained, particularly in areas where rabies is enzootic, even though the animal is considered to be healthy at the time of exposure. Such cases may be treated as category II or III.

Post-exposure treatment, which consists of local treatment of the wound, followed by vaccine therapy (with or without rabies immunoglobulin) should be initiated immediately with contacts of categories II and III. Treatment may be discontinued if the animal involved (dog or cat) remains healthy throughout an observation period of 10 days; or if the animal is killed humanely and found to be negative for rabies by laboratory examination. Any biting animal suspected of being rabid should be immediately killed humanely and tissues examined using appropriate laboratory technique(s). Modification of the recommended procedures would be indicated in a rabies-free area where animal bites are encountered. In areas where canine or wildlife rabies is epizootic, adequate laboratory and field experience, indicating that there is no infection in the species involved, may justify local health authorities in not recommending specific anti-rabies treatment.

The indication for post-exposure vaccination with or without rabies immune globulin depends on the type of contact with the rabid animal.

Types of contact are:

category III – single or multiple transdermal bites or scratches, contamination of mucous membrane with saliva from licks; exposure to bat bites or scratches

For category I no treatment is required, whereas for category II immediate vaccination and for category III immediate vaccination and administration of rabies immune globulin are recommended in addition to immediate washing and flushing of all bite wounds and scratches. Depending on vaccine type, the post-exposure schedule prescribes intramuscular doses of 1 ml or 0.5 ml given as four to five doses over four weeks. For rabies-exposed patients who have previously undergone complete pre-exposure vaccination or post-exposure treatment with cell-derived rabies vaccines, two intramuscular doses of a cell-derived vaccine separated by three days are sufficient. Rabies immune globulin treatment is not necessary in such cases. The same rules apply to persons vaccinated against rabies who have demonstrated neutralizing antibody titres of at least 0.5 IU/ml.

In order to reduce the cost of post-exposure treatment, intradermal multi-site regimens using a fraction of the intramuscular volume per intradermal inoculation site have been developed. Purified Vero cell vaccine has been given intradermally to more than 70 000 recipients in Thailand, where it has been in routine use for several years. Intradermal rabies vaccination is also recommended by the ministries of health of Sri Lanka (since 1995) and the Philippines (since 1997). In each of these countries the introduction of this route for post-exposure treatment has permitted the discontinuation of the local production of vaccines prepared on brain tissue. Only the cell-derived vaccines that meet the WHO requirements regarding safety, potency and efficacy for this application may be considered for intradermal use. Although rabies vaccines are usually administered under qualified medical supervision, field experience from routine infant immunization programmes with other intradermally injected vaccines highlights the potential difficulties in assuring proper delivery. This emphasizes the need for appropriate staff training to ensure correct storage, reconstitution and injection. Provided that a correct sterile technique is used, the remaining doses may be kept in the vial at 2–8°C and used for another patient within six hours after reconstitution.

Tissue-culture or purified duck-embryo vaccines of potency at least 2.5 IU per single intramuscular immunizing dose should be applied according to the following schedules.

Intramuscular schedules

One dose of the vaccine should be administered on days 0, 3, 7, 14 and 30. All intramuscular injections must be given into the deltoid region or, in small children, into the anterolateral area of the thigh muscle. Vaccine should never be administered in the gluteal region.

Abbreviated multisite schedule

In the abbreviated multisite schedule, the 2-1-1 regimen, one dose is given in the right arm and one dose in the left arm at day 0, and one dose applied in the deltoid muscle on days 7 and 21. The 2-1-1 schedule induces an early antibody response and may be particularly effective when post-exposure treatment does not include administration of rabies immunoglobulin.

Intradermal schedule

WHO recommended the following intradermal regimen and vaccines for use by the intradermal route:

For 2-site intradermal method (2-2-2-0-1-1)

Brain-tissue vaccines

The use of brain-tissue vaccines should be discontinued. WHO does not recommend any schedule using brain-tissue vaccine. National authorities should recommend a schedule of immunization that has been shown to induce an adequate level of protection when brain tissue vaccines are available in that country.

Combined immunoglobulin-vaccine

Combined immunoglobulin-vaccine treatment was considered in the eighth report of the WHO Expert Committee as the best specific systemic treatment available at that time for the post-exposure prophylaxis of rabies in humans, although experience indicated that vaccine alone was sufficient for minor exposures (category II). Immunoglobulin should be given in a single dose of 20 IU per kg of body weight for human anti-rabies immunoglobulin, and 40 IU per kg of body weight for heterologous (equine) immunoglobulin; the first dose of vaccine should be inoculated at the same time as the immunoglobulin, but in a different part of the body. Sensitivity to heterologous immunoglobulin must be determined before it is administered. The physician should be prepared to deal with anaphylactic shock reactions. Administration of rabies immunoglobulin (RIG) should be infiltrated into the depth of the wound and around the wound as much as anatomically feasible. Any remainder should be injected at an intramuscular site distant from that of vaccine inoculation e.g. into the anterior thigh.

Treatment should be started as early as possible after exposure, but in no case should it be denied to exposed persons whatever time interval has elapsed.

Local treatment of wounds

Local treatment of wounds involving possible exposure to rabies – recommended in all exposures.